Methyl isothiocyanate

Endpoint summary

Description of key information

Based on the physical and chemical properties, MITC is well absorbed after oral, dermal or inhalation exposure.
Short description of key information on bioaccumulation potential result: 
In mice after i.p. administration, 80% of the radiolabeled-MITC are excreted in urine and 6% are retained in the carcass. MITC is metabolized in rats to the mercapturate N-acetyl-S-(N-methylthiocarbamoyl) cysteine via the glutathione conjugate S-(N-methylcarbamoyl)-GSH which serves as a potential carrier for later release of the MITC moiety, whereas from mice the mercapturate is a minor metabolite.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

The following remarks on the toxicokinetics of MITC are based on the available studies. Four experimental toxicokinetic studies were available on MITC. Moreover, as per REACH guidance document R7.C (May 2008), information on absorption, distribution, metabolisation and excretion may be also deduced from the physicochemical properties, including:

-Molecular weight: 73.12 g/mol

-Water solubility: 7.9 g/L (20°C)

-Partition coefficient Log Kow: 1.3 (20°C)

-Vapour pressure: 3000 Pa (25°C)

 

ABSORPTION

The moderate log Kow, high water solubility and low the molecular mass of MITC are in the range suggestive of absorption from the gastro-intestinal tract subsequent to oral and dermal exposure. That is confirmed in the acute toxicity studies : MITC is very toxic if swallowed in mice study (LD50 = 930 mg/kg) and toxic in contact with skin of rats (LD50 = 174 mg/kg).

The moderate vapour pressure, moderate log kow and the high water solubility are favourable of inhalation absorption. Indeed MITC is very toxic if inhaled in rat (LC50(1h)=1.9mg/L).

 

DISTRIBUTION

As a small molecule a wide distribution of MITC is expected.

According to the Lam's study (1993), radiocarbon from [(14)CH3]-MITC is widely distributed in the tissues at 6, 24, and 48h post treatment, liver and kidney retained higher (14)C-residues.

METABOLISM

The major metabolites from rats are S-(N-methylthiocarbamoyl)glutathione in the bile and S-(N-methylthiocarbamoyl)mercapturic acid in the urine (26% of the 14C in urine after 48 h), whereas from mice the mercapturate is a minor metabolite (2.1 % of the 14C in urine after 48 h). Methylamine is not a major urinary metabolite following treatment with MITC, it contributed only about 2% of the 14C in urine in both species. Detoxification by conjugation with glutathione appears to involve nonenzymatic reaction (Lam et al., 1993).

 

EXCRETION

MITC is probably excreted in the urine, because it is a water-soluble substance with a low molecular weight (below 300).

It is confirmed in the Lam's study (1993): male Swiss-Webster mice were treated intraperitoneally with radiolabeled-MITC at 0.05 mmol/kg bw (4 mg/kg). Eighty percent of the radiocarbon were excreted in the urine within 48 h. Feces are a minor route of excretion, accounting for only 4.8%. recovery of (14)CO2 was 3.8% of the administered dose. Radiocarbon in whole carcasses 48 h after dosing was 6%, and 85-90% of these residues were refractory to extraction by methanol.

Groups, each of five Wistar rats, received orally 10 mg MITC per animal in 1 ml of olive oil. Urine was collected for 24 hr. Renal excretion of the N-acetyl-S-(N-methylthiocarbamoyl)-L-cysteine as a percentage of the dose administered was 47+10% (Mennicke et al, 1987).